In the eight years since recognition of the first cases of AIDS, the disease has become pandemic and knowledge of the epidemiology of the causative agent, the human immunodeficiency virus, (HIV) and of risk factors for HIV acquisition has accrued rapidly. Nonetheless, relatively little is known about rates of HIV transmission or the potential for proposed cofactors to enhance transmission efficacy. Retrospective data suggest that some types of scxual activitics (e.g., relatively traumatic sexual activity such as receptive rectal intercourse) or sexually transmitted genital ulcer discases (syphilis, genital herpes, chancroid) are risk factors for HIV acquisition. We propose to prospectively study the transmission and acquisition of HIV among patients and their sexual partners attending an inner-city STD clinic with a relatively high (>5%) prcvalencc of HIV infection to address the following specific aims: 1) to determine the contribution of genital ulceration to risk for HIV acquisition; 2) to determine thc contribution of genital ulccration to risk for HIV transmission; 3) to compare the etiology of genital ulceration among patients with and without concomitant HIV infection; 4) to evaluate the effect of concomitant HIV infections on the clinical manifestations, recurrcnce rates, and frequency of asymptomatic shedding in patients with genital herpes; 5) to evaluate the effect of concomitant HIV infection on the presenting clinical manifestations of syphilis and the scrologic responsc to currently recommended therapy and; 6) to characterize the potential of genital ulcer discases (syphilis, genital herpes, chancroid, and ulcers without discernible microbial etiology) to act as sites for HIV transmission through quantification and enumeration of type-specific lymphocytes in genital ulcer bases and exudates. To accomplish these goals, over a 5 year period we will enroll, evaluate, and follow in excess of 2,000 patients (1,000 with and 1,000 without genital ulcers) and their sexual partners (slightly more than I partner per patient), providing data for determination of HIV transmission and acquisition on more than 2,000 relatively high risk couples. All participants will be evaluated using comprehensive questionnaires to determine possible behavioral and biologic contributors to risk for HIV transmission and acquisition. Laboratory investigations will include etiologic evaluation of genital ulcer discase, scrologic screening for STD and HIV infections, and determination of circulating T-helper (T4+) and Tsuppressor (T8+) lymphocyte concentrations. Data collected as part of this study will be analyzed using bivariate and multivariate techniques to calculate and model the contribution of genital ulcers, as well as other behavioral and biologic factors, as cofactors which enhance the efficiency of HIV transmission to uninfected sexual partners.